Preimplantation development encompasses the period from fertilization to implantation. These early embryos are the source of Embryonic stem (ES) cells and the locus of nuclear reprogramming. Therefore, the molecular study of these early embryos is very important for stem cell biology and its potential therapeutic applications to aging and dysfunctional organs/tissues. Our goal is to apply systematic genomic approaches to these early embryos and to understand their regulation of gene expression. We carried out DNA microarray-based global expression profiling of all preimplantation stages in mouse, which revealed and characterized the distinctive patterns of maternal RNA degradation and two major transient waves of de novo transcription: zygotic genome activation (ZGA) and mid-preimplantation gene activation (MGA). Through these analyses, we identified a number of genes that show unique expression patterns. We have demonstrated that one of them, named Zga1, is expressed exclusively in 2-cell mouse embryos and ES cells and plays a critical role in the progression of preimplantation development. We also found that a gene called Chuk shows constant RNA levels throughout preimplantation development and can be used as an internal standard suitable for quantitative RT-PCR (Falco et al., 2006). We also developed a technique to do large-scale Whole Mount In Situ Hybridization (WISH), which allows us to reveal the spatial expression patterns of 91 genes in mouse preimplantation embryos (Yoshikawa et al., 2006). We are currently studying the functions of these genes in details.